MIF ENZYMATIC INHIBITION

MIF 酶抑制

• 批准号: 8170587
• 负责人: ELIAS LOLIS
• 金额: $ 0.27万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170587
• 关键词: Active Sites; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Binding; Catalytic Domain; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Disease; Funding; Glucocorticoids; Grant; Immunology; Inflammation; Inflammatory; Institution; Malignant Neoplasms; Migration Inhibitory Factor; Nature; Physiological; Rattus; Research; Research Personnel; Resolution; Resources; Septic Shock; Source; Structure; United States National Institutes of Health; cytokine; insulin secretion; phenylpyruvate tautomerase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine that counteracts the anti-inflammatory activities of glucocorticoids (Calandra and Bucala J. Inflammation 47, pg. 39, 1995). Excessive MIF activity has been implicated in a number of diseases, including septic shock (Bernhagen et al. Nature 365, pg. 756, 1993), arthritis Mikulowska et al. J. Immunology 158, pg. 5514, 1997) and cancer (Ren et al. Ann. Surg. 242, pg. 55,2005). MIF has also been found to enhance insulin secretion in rats (Waeber et al. PNAS 94, pg. 4782, 1997). Not only is MIF a cytokine, but it also has catalytic activity. Although all of its known catalytic activities involve non-physiological substrates, inhibiting the catalytic active-site inhibits its pro-inflammatory function (Lubetsky et al. J. Biol. Chem. 277, pg.24976, 2002). We hope to obtain high-resolution structures of compounds bound to MIF in this catalytic site.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 巨噬细胞迁移抑制因子 (MIF) 是一种促炎细胞因子，可抵消糖皮质激素的抗炎活性（Calandra 和 Bucala J. Inflammation 47，第 39 页，1995）。过度的 MIF 活性与许多疾病有关，包括感染性休克（Bernhagen 等人，Nature 365，第 756 页，1993）、关节炎 Mikulowska 等人。 J. 免疫学 158，第 158 页。 5514, 1997）和癌症（Ren 等人 Ann. Surg. 242，第 55 页，2005）。还发现 MIF 可以增强大鼠的胰岛素分泌（Waeber 等人，PNAS 94，第 4782 页，1997）。 MIF不仅是一种细胞因子，而且还具有催化活性。尽管其所有已知的催化活性都涉及非生理底物，但抑制催化活性位点会抑制其促炎功能（Lubetsky et al. J. Biol. Chem. 277, pg.24976, 2002）。我们希望获得在此催化位点与 MIF 结合的化合物的高分辨率结构。